This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We will recruit patients with moderate to severe COPD who have either had a COPD exacerbation within the past year or who use supplemental oxygen. Eligible subjects will be randomized to receive either a macrolide antibiotic, azithromycin, or placebo for one year. The primary outcome will be to determine whether or not taking azithromycin daily will decrease the frequency or severity of COPD exacerbations. We will follow subjects monthly, either by phone or by clinic visit, while they receive their assigned study treatment and at a clinic visit one month after they stop the study treatment. We will also collect blood at certain clinic visits and the one-month follow-up clinic visit to determine the effect of chronic macrolide treatment on specific blood products.